Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion
- Authors
- Mun, Se Hwan; Bae, Seyeon; Zeng, Steven; Oh, Brian; Chai, Carmen; Kim, Matthew Jundong; Kim, Haemin; Kalliolias, George; Dahia, Chitra Lekha; Oh, Younseo; Kim, Tae-Hwan; Ji, Jong Dae; Park-Min, Kyung-Hyun
- Issue Date
- 20-10월-2021
- Publisher
- SPRINGERNATURE
- Citation
- BONE RESEARCH, v.9, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- BONE RESEARCH
- Volume
- 9
- Number
- 1
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/136022
- DOI
- 10.1038/s41413-021-00162-0
- ISSN
- 2095-4700
- Abstract
- Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone erosion. Macrophage colony stimulating factor (M-CSF) is abundant in rheumatoid arthritis (RA). However, the role of M-CSF in arthritic bone erosion is not completely understood. Here, we show that M-CSF can promote osteoclastogenesis by triggering the proteolysis of c-FMS, a receptor for M-CSF, leading to the generation of FMS intracellular domain (FICD) fragments. Increased levels of FICD fragments positively regulated osteoclastogenesis but had no effect on inflammatory responses. Moreover, myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis model. The FICD formed a complex with DAP5, and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathway and enhancing NFATc1 protein expression. Moreover, targeting the MNK1/2 pathway diminished arthritic bone erosion. These results identified a novel role of c-FMS proteolysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.